For many blood cell malignancies such as certain types of leukaemia and multiple myeloma, haematopoietic stem cell (HSC) transplantation is an important therapeutic option. Furthermore, these cells are extensively used in research and in the development of urgently needed treatments for other diseases, including HIV and multiple sclerosis. The use of HSCs is however severely constrained by the limited expansion of these cells: Current cell culturing techniques result in insufficient quality and quantity of stem cells.
Many studies have tried to stimulate HSC expansion by experimenting with cytokine cocktails in cell culture media. Although these combinations of growth factors are able to increase the amount of HSCs, this happens at the cost of cell maturation: many of the cells in the final culture have lost their stem cell properties, in other words have lost their ‘stemness’, and thus their use for treatment and R&D. This hampers treatment outcomes and R&D activities which also become excessively expensive and inefficient.
Beyond a doubt, improving HSC expansion has a huge societal benefit: HSC transplantation will be cheaper and applicable for many more patients. The cost reduction is of particular interest since, according to a recent report of the Agency for Health Care Research and Quality, HSC transplantation has generated the most rapid increase in total hospital costs over the last decade. Of particular interest is the use technology for the expansion of HSCs from umbilical cord blood (UCB), a highly promising novel source of HSCs. Unfortunately, still 90% of patients referred for UCB transplantation are ineligible due to the limited number of stem cells available in a typical UCB unit.
The present disclosure for the expansion of these cells could provide a solution for this unmet medical need. Moreover, the improved availability of HSCs will drive research in stem cell biology and the development of novel treatment options for diseases such as HIV and multiple sclerosis.
Besides societal benefits there is also a significant commercial opportunity. US based stem cell research accounted for US $820 million in expenditures in 2005, with 10% (US $82 million) allocated for consumables such as media and culture suppliers. Spending on stem cell research is expected to reach US $2 billion by 2015 with approximately 20% (about US $400 million) allocated for consumables [Bioinformatics, 2009]. Multinational pharmaceutical companies increasingly turn to the development of stem cell therapies which indicates the presence of significant opportunities in this emerging market [Datamonitor, 2011].
The present invention intends to disclosure the role of RET during haematopoiesis, leading to the discovery that neurotrophic factors have a strong beneficial effect on HSC survival, function and expansion.